Devices and methods have been developed for the administration of pharmaceuticals at desired sustained levels by absorption through the skin. Transdermal delivery systems are available, or have been proposed, for many pharmaceutical agents. Typically, devices used in such techniques (often referred to as "patches") are attached to the skin of a patient, usually adhesively. The active agent is caused to diffuse from the device through the skin for absorption into the bloodstream. Upon absorption into the bloodstream, the agent is carried throughout the body of the patient.
Numerous techniques have been proposed to control the rate of release of pharmaceutical agents in transdermal delivery systems. For example, in U.S. Pat. Nos. 4,314,557 and 4,460,472, systems are disclosed which control the rate of release of an agent by the rate of which a drug solute phase dissolves in a polymer matrix phase. In U.S. Pat. No. 4,379,454, a drug and an absorption enhancer are said to be contained in a solid, semi-solid or gel matrix phase.
U.S. Pat. No. 4,409,206 describes a transdermal release system using a skin-compatible polyacrylate, which swells with water and may contain a hydrophilic component to regulate the rate of release.
U.S. Pat. No. 4,624,665 suggests sealing the skin with an occlusive layer, and transporting a desired dosage of an active agent across the layer from a rate controlling system.
U.S. Pat. No. 4,645,502 discloses an encapsulated permeation enhancer and a dry active agent within an aqueous gelled reservoir.
U.S. Pat. No. 4,690,683 discloses an active pharmaceutical dispersed in a polymeric material to form, by cross-linking, a matrix. As an alternative, a solution of the active pharmaceutical may be dispersed in the matrix prior to cross-linking, in which case, the patent says, "micro reservoirs" of the drug are formed in the matrix. A suggestion is also made in this patent of the possibility of incorporating a buffering agent into the matrix.
U.S. Pat. No. 5,149,538, discloses inclusion, in a transdermal delivery system for opioids, of an encapsulated antagonist as a control on the rate of delivery of the opioid.